Collaborative Review – Prostatic DiseaseThe Controversial Relationship Between Benign Prostatic Hyperplasia and Prostate Cancer: The Role of Inflammation
Introduction
Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are significant health concerns that may become increasingly prevalent in the coming years in relation to the gradual aging of the population [1], [2], [3]. PCa is the leading cause of nonskin cancer among men worldwide and, after lung cancer, is the second most common cause of death from cancer in men in the United States [4]. BPH represents the most common urologic disease among elderly males, affecting about one-quarter of men in their 50 s, one-third in their 60 s, and about half of octogenarian men [5], [6].
BPH and PCa form in different areas of the prostate. The former is known to develop from the transitional zone (TZ) and central zone of the gland, while the latter develops from the peripheral zone (PZ). Only in about 20% of cases do the conditions coexist in the same zone [7]. BPH and PCa are considered chronic diseases, with early initiation and slow progression. BPH starts as a simple micronodular hyperplasia, evolving into a macroscopic nodular enlargement that gradually translates into a clinical entity. Similarly, PCa develops through early and late precancerous histologic modifications [3]. Furthermore, although there is no clear molecular and genetic relationship between BPH and PCa and they present two distinct pathogenetic pathways, epidemiologic studies suggest that because their incidence and prevalence rise with increased age, both conditions are hormone dependent and are associated with prostatic inflammation, which can represent a common denominator [1].
Neither BPH nor PCa is a single disease; rather, they express different features in terms of epithelial-to-stromal–ratio Gleason score or cancer volume. These aspects are often neglected in reference to prostate inflammation. We understand the difficulty in considering too many variables, but we are also concerned with the limitations of it.
Chronic inflammation secondary to infectious agents, to the exposure of other environmental factors, or to a combination of both is involved in the pathogenesis of about 20% of human cancers, including stomach, liver, and large intestine [8], [9]. Epidemiologic, histopathologic, and molecular pathologic studies provide the emerging evidence of the possible role of prostatic inflammation as a crucial part of PCa pathogenesis and progression [10].
The molecular and cellular mechanisms involving stromal and epithelial components of the prostate leading to BPH remain unclear, notwithstanding a causative role of prostatic inflammation in the pathogenesis of BPH, which was first suggested in 1937 [11]. Today, although it is not yet defined when and why chronic inflammation occurs, it has been hypothesised that BPH is an immune-mediated inflammatory disease [5], [12], [13], [14], [15], and recent clinical trials have also suggested a relationship between prostatic inflammations and lower urinary tract symptoms (LUTS) related to BPH [16], [17], [18]. Epidemiologic evidence of a link between the use of anti-inflammatory agents and the risk of cancer led to novel therapeutic approaches that were proposed as a new frontier in the prevention and treatment of PCa [1], [8]. In BPH patients, the relation between LUTS and inflammation is well known [2], as different prostatic conditions, including BPH, benefit from antibacterial and anti-inflammatory treatment.
We also acknowledge the lack of a standard definition of prostatic inflammation that probably exists only in the classification of chronic pelvic pain. The definition is clearly useful for clinical purposes but would be meaningless in research on prostate immunology. Inflammation is usually described in basic science papers in terms of cellular effectors and released mediators.
This is a nonsystematic review to evaluate the most recent evidence with respect to prostatic inflammation as a major pathway in the controversial relationship between BPH and PCa and discusses its potential clinical implications.
Section snippets
Evidence acquisition
The National Library of Medicine Database was searched for relevant articles published between January 2000 and October 2010 using the following Patient population, Intervention, Comparison, Outcome (PICO) terms: male, inflammation, benign prostatic hyperplasia, prostate cancer, diagnosis, prognosis, progression, treatment, and prevention. In addition, sources in the reference sections of the publications identified were added to the list. English-language text was not a specific parameter;
Prostatic inflammation
The presence of chronic histologic inflammation is a well-known finding in biopsy and surgical specimens of prostate tissue in patients with and without LUTS or prostatitis [6], [19].
Conclusions
Although we do not completely understand the pathways of chronic prostatic inflammation, the evidence summarised in this review suggests the important role of inflammatory infiltrates and their mediators in the development of chronic prostatic diseases such as BPH and PCa. Prostatic inflammation should not be considered only as an occasional histologic finding in prostate specimens but as a possible link between prostatitis, BPH, and PCa. Chronic prostatic inflammation may result from the
References (79)
- et al.
Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review
Eur Urol
(2009) - et al.
Benign prostatic hyperplasia and its aetiologies
Eur Urol Suppl
(2009) - et al.
Inflammation and chronic prostatic diseases: evidence for a link?
Eur Urol
(2007) - et al.
Is benign prostatic hyperplasia (BPH) an immune inflammatory disease?
Eur Urol
(2007) - et al.
Should we investigate prostatic inflammation for the management of benign prostatic hyperplasia?
Eur Urol Suppl
(2009) - et al.
Anti-inflammatory drugs, antioxidants, and prostate cancer prevention
Curr Opin Pharmacol
(2009) - et al.
Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue
Lab Invest
(2003) - et al.
The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial
Eur Urol
(2008) - et al.
The impact of acute or chronic inflammation in baseline biopsy on the risk of clinical progression of BPH: results from the MTOPS study
J Urol
(2005) Inflammation and benign prostatic hyperplasia
Urol Clin North Am
(2008)